Carboxylesterase (CES) (CES)

The Carboxyl/cholinesterase family represents a diverse group of serine hydrolases, including major drug-metabolizing enzymes such as Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2), as well as Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) (Source: UniProt, NCBI). These enzymes are defined by a conserved alpha/beta-hydrolase fold and a catalytic triad (Ser-Glu/Asp-His) that enables the efficient hydrolysis of a wide array of endogenous and exogenous esters, amides, and thioesters (Source: PubMed, PMID: 15603504). In human physiology, CES enzymes are primarily localized in the liver and gastrointestinal tract, where they serve as the primary gateway for the activation of many ester-based prodrugs, such as the antiviral oseltamivir and the chemotherapeutic irinotecan (Source: FDA, StatPearls). Beyond drug metabolism, members of this family like AChE are critical for regulating neurotransmission at cholinergic synapses, making them primary therapeutic targets for Alzheimer's disease treatments like donepezil (Source: NIH, PubChem). The activity of these enzymes is a major determinant of drug bioavailability and therapeutic efficacy; however, significant inter-individual variability exists due to genetic polymorphisms and susceptibility to inhibition by environmental toxins like organophosphates (Source: Wikipedia, Journal of Biological Chemistry). Understanding the substrate specificity and tissue distribution of this family is essential for optimizing drug design and predicting potential toxicological outcomes in clinical pharmacology.

Other names

Carboxyl/cholinesterase familyCarboxylic-ester hydrolaseB-esteraseSerine esteraseAli-esteraseMonoglyceride lipase

Carboxylesterases facilitate the hydrolysis of various ester-containing prodrugs into their active pharmacological forms (e.g., converting oseltamivir to oseltamivir carboxylate). In the context of cholinesterases (AChE/BChE), drugs often act as inhibitors to increase the residence time of acetylcholine in the synaptic cleft to treat cognitive symptoms of dementia.